• Korean Journal of Pharmacognosy
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• v.23 no.4
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• pp.259-263
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• 1992

The neuroprotective effect of betaine, one of the components of Lycii Fructus, on glutamate-induced neurotoxicity in primary cultured chicken brain cells were examined. Betaine was found to attenuate glutamate-induced neurotoxicity at the concentration of $5{\sim}10{\;}mM$ in both morphological and chemical aspects. The pretreatment of chicken brain cells with $5{\sim}10{\;}mM$betaine for 2hr at the 12 th day of culture before the 40min-exposure to $500\;{\mu}M$ glutamate significantly increased the survival rate of nerve cells in chicken brain. Betaine could also raise the decreased LDH-level in chicken brain cells which were induced neurotoxicity with $100\;{\mu}M$ glutamate. LDH value was decreased to 63% of control level in chicken brain cells at the time of 48 hr after the exposure to glutamate. However, the pretreatment of chicken brain cells with 5 mM betaine for 2 hr before the exposure to glutamate prevent the decrease of LDH in cells showing 90% of control level. Nevertheless, the remarkable neuroprotective effect of betaine on the glutamate-induced neurotoxicity in cultured chicken brain cells could not be observed when betaine was simultaneously administrated with glutamate.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.46-46
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• 1993

The neuroprotective effect of betaine, one of the , components of Lycii Fructus, on glutamate-induced neurotoxicity in primary cultured chicken brain cells were examined. Betaine was found to attenuate glutamate-induced neurotoxicity at the concentration of 5-10 mM in both morphological and chemical aspects. The pretreament of chicken brain cells with 5-10 mM betaine for 2 hr at the 12th day of culture before the 40 min-exposure to 500${\mu}$M glutamate significantly increased the survival rate of nerve cells in chicken brain. Betaine could also raise the decreased LDH-level due to the neurotoxicity induced with 100${\mu}$M glutamate in chicken braill cells. LDH value was decreased to 63％ of control level in chicken brain cells at the time of 48 hr after the exposure to glutamate. However, the pretreament of chicken brain cells with 5 mM betaine for 2 hr before the exposure to glutamate could prevent the decrease of LDH-level in brain cells showing 90％ of control level. Nevertheless, tile remarkable neuroprotective effect of betaine on the glutamate-inducer in neurotoxicity in cultured chicken brain cells could not be observe when betaine was simultaneously administered with glutamate.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.343-347
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• 1994

Effects of betaine on glutamate-induced neurotoxicity were examined on primary culturs of chicken embryonic brain cells and on rat cortical cultures. Betaine was found to attenuate glutamate-induced neurotoxicity both morphologically and biochemically. A 30 min exposure of chicken embryonic brain cells cultured for 12 days to 500 .mu.M glutamate produced wide-spread acute neuronal swelling and neurtic fragmentation. A 2-h pretreatment of cultured chicken embryonic brain cells with i mM betaine prior to a 30 min exposure to 500 , mu, M glutamate significantly raised the survival rate of neurons in the culture. When chicken embryonic brain cells were pretreated for 2 h with i mM betaine followed by exposure to 100 .mu.M glutamate for 42 h, lactate dehydrogenase levels within the cells remained at 62% of .mu.M untreated control values while glutamate-treated control fell to 0% lactate dehydrogenase. Betaine also exerted attenuating effects on N-methyl-D-asparte-, kainate-and quisqualate-induced neurotoxicity in a similar manner to that observed with glutamate. Similar neuroprotective effects of betaine with rat cortical cultures.

• Natural Product Sciences
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• v.18 no.1
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• pp.26-31
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• 2012

Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

• Natural Product Sciences
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• v.15 no.3
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• pp.125-129
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• 2009

Neurodegenerative diseases such as Alzheimer's disease, stroke, and Parkinson's disease, are caused by neuronal cell death. Apoptosis, oxidative stress, inflammation, excitotoxicity or ischemia are discussed to play a role of neuronal cell death. In order to find the candidate of neuroprotective agent, neuroprotective activity of some medicinal plants was investigated with in vitro assay system using glutamate-induced neurotoxicity in primary cultures of rat cortical cells. The aqueous methanolic extracts of twenty-seven medicinal plants were evaluated the protective effects against glutamate-injured excitotoxicity in rat cortical cells at the concentration of 50 $\mu$g/ml and 100 $\mu$g/ml, respectively. Among them, extracts of Lonicera japonica, Taraxacum platycarpum, Polygonum aviculare, Gardenia jasminoides, Forsythia viridissima, Lygodium japonicum, Panax notoginseng, Akebia quinata, Anemarrhena asphodeloides and Phellodendron amurense showed significantly neuroprotective activities against glutamate-induced neurotoxicity in primary rat cortical cells.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.47-56
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• 1998

In the present study, we assayed a number of compounds isolated from Panax ginseng C. A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rbl and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was significantly reduced by pretreatment with Rbl and Rgl. Ginsenosides Rbl and Rg3 inhibited the overproduction of nitric oxide which routinely follows glutamate neurotoxicity and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rbl and Rg1 exerted significant neuroprotective effects on cultured cortical cells. As such, these compounds may be efficacious in protecting neurons from oxidative damage produced by exposure to excess glutamate.

• Korean Journal of Oriental Medicine
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• v.4 no.1 s.4
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• pp.99-114
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• 1998

The effect of herbal medicine on glutamate mediated neurotoxicity was studied in mouse neurons in primary culture. Immature cerebral cortex neurons (ED14) were maintained for up to 2 weeks in vitro, and we investigated the expression pattern of neuron differentiation and cytotoxicity of cell death, including LDH activity. Neuronal maturation initiated on day 7 and the susceptibility to glutamate-induced cell death was highly sensitive on Day 11 (Fig. 1). Thus, the exposure of the neurons to glutamate caused a dose$(0.1mM{\sim}1mM)$ and time$(4h{\sim}24h)$-dependent neurotoxicity(Fig. 4). Glutamate-induced neurodegeneration was prevented by Shipchondaebotang(SD), Yollyounggobondan(YG), Yugmijihwangwon(YJ) and the death of neurons exposed to glutamate was blocked by the NMDA receptor antagonist MK-801 (Fig. 5).

• Natural Product Sciences
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• v.15 no.1
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• pp.32-36
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• 2009

Glutamate causes neurotoxicity through formation of reactive oxygen species and activation of mitogen-activated protein kinase (MAPK) pathways. MAPK phosphatase-1 (MKP-1) is one of the phosphatases responsible for dephosphorylation/deactivation of three MAPK families: the extracellular signal-regulated kinase-1/2 (ERK-1/2), the c-Jun N-terminal kinase-1/2 (JNK-1/2), and the p38 MAPK. In this report, the potential involvement of MKP-1 in neuroprotective effects of curcumin, the active ingredient of turmeric (Curcuma longa), was examined using HT22 cells. Glutamate caused cell death and activation of ERK-1/2 but not p38 MAPK or JNK-1/2. Blockage of ERK-1/2 by its inhibitor protected HT22 cells against glutamate-induced toxicity. Curcumin attenuated glutamate-induced cell death and ERK-1/2 activation. Interestingly, curcumin induced MKP-1 activation. In HT22 cells transiently transfected with small interfering RNA against MKP-1, curcumin failed to inhibit glutamate-induced ERK-1/2 activation and to protect HT22 cells from glutamate-induced toxicity. These results suggest that curcumin can attenuate glutamate-induced neurotoxicity by activating MKP-1 which acts as the negative regulator of ERK-1/2. This novel pathway may contribute to and explain at least one of the neuroprotective actions of curcumin.

• International Journal of Oral Biology
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• v.49 no.1
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• pp.10-17
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• 2024

Glutamate-mediated oxidative stress causes neuronal cell death by increasing intracellular Ca²⁺ uptake, reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) activation, and translocation of apoptosis-inducing factor (AIF) to the nucleus. In the current study, we demonstrated that corydaline exerts potent neuroprotective effects against glutamate-induced neurotoxicity. Treatment with 5 mmol/L glutamate increased cellular Ca²⁺ influx, ROS generation, MAPK activation, and AIF translocation. In contrast, corydaline treatment decreased cellular Ca²⁺ influx and ROS generation. Western blot analysis revealed that glutamate-mediated MAPK activation was attenuated by corydaline treatment. We further demonstrated that corydaline treatment inhibited the glutamate-mediated translocation of AIF to the nucleus. We propose that corydaline is a promising lead structure for the development of safe and effective neuroprotectants.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.164-170
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• 2001

Glutamate receptors-mediated excitoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fanschinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a $Ca^{2+}$channel blockers on excitatory amino acids (EAAS)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$), N-methyl-D-aspartate (NMDA; 1 ${m}M$) and kainate (100$\mu\textrm{m}$)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate release into medium induced by NMDA (1 ${m}M$) and kainate (100$\mu\textrm{m}$), which was measured by HPLC. And fangchinoline (5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of $Ca^{2+}$influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions.